Developmental Cancer Therapeutics Program ABSTRACT The Developmental Cancer Therapeutics (DCT) Program has evolved considerably since 2012 with an increased focus on both solid tumor oncology and the translational aspects of advancing basic science into early-phase clinical trials in rapid fashion. Under the leadership of David Horne, PhD and Edward Newman, PhD, the central theme and overarching goal of DCT are the in-house development of novel, molecularly targeted therapies and drug delivery systems for intractable cancers. Although DCT has continued the Program's long- standing strength in evaluating cancer therapeutics developed through industry partnerships, the emphasis of the DCT Program is to advance important basic discoveries made at the City of Hope Cancer Comprehensive Center (COHCCC). To this end, DCT has established clear scientific goals that fall under three central themes: 1) Support target-directed drug development by identifying and validating new molecular cancer targets/pathways and developing corresponding pharmacological agents; 2) Develop novel drug delivery platforms to improve specificity and efficacy of clinical outcomes; and 3) Translate basic discovery and preclinical studies into early-phase clinical trials. The DCT program extends across eight departments and encompasses a total of 29 Members, of which 12 are basic researchers and 17 are clinicians/clinician scientists. Through the Program, close intra- and inter-programmatic collaborations are fostered among basic scientists and clinical investigators, which in turn has yielded an increase in the number of COH-initiated agents currently under clinical investigation. During the previous grant period, significant infrastructure has been established for the creation of a strong translational research program with greater focus on solid tumor oncology, resulting in a continuous flow of new therapeutic approaches poised for early-phase clinical trials. The emphasis is on speed and precision medicine. With only GLP toxicity studies and some formulation work contracted outside, the DCT Program can rapidly translate discoveries to the clinic. This Program has been further enhanced by the strategic recruitment of key faculty (Chen, Fakih, Fong, Gold, and Salgia), implementation of a drug discovery pipeline, and cGMP manufacturing capability for small molecule drugs, such as COH29, through COH?s in-house Chemical cGMP Synthesis Facility. During the next funding period, we anticipate robust translation of our new therapeutic approaches from the discovery phase to first-in-human clinical trials and continued close collaboration with other regional and national Comprehensive Cancer Centers. Membership: 29 Program Members representing 8 basic and clinical departments Publications: 503 total. 20.1% intra-programmatic; 36.4% inter-programmatic; 41.2% inter-institutional Funding: $4,751,305 peer-reviewed; $1,794,235 of which is NCI funding